Background Cumulative evidences demonstrated the aberrant overexpression of Small Nucleolar RNA Host Gene 12 (SNHG12) in diverse human cancer. However, the expression status and involvement of SNHG12 in renal cell carcinoma is still elusive. Methods The expression of SNHG12 was determined by q-PCR. The transcriptional regulation was interrogated by luciferase reporter assay. Cell viability was measured with CCK-8 kit. The anchorage-independent was evaluated by soft agar assay. Cell apoptosis was analyzed by Annexin V/7-AAD double staining. The migration and invasion were determined by trans-well assay and wound scratch closure. The in vivo tumor growth was monitored in xenograft mice model. Protein expression was quantified by immunoblotting. Results SNHG12 was aberrantly up-regulated in renal carcinoma both in vivo and in vitro. High expression of SNHG12 associated with poor prognosis. Deficiency of SNHG12 significantly suppressed cell viability, anchorage-independent growth and induced apoptosis. In addition, SNHG12 silencing inhibited migrative and invasive in vitro and xenograft tumor growth in vivo. Mechanistically, SNHG12 modulated HIF1α expression via competing with miR-199a-5p, which consequently contributed to its oncogenic potential. MiR-199a-5p inhibition severely compromised SNHG12 silencing-elicited tumor repressive effects. Conclusion Our data uncovered a crucial role of SNHG12-miR-199a-5p-HIF1α axis in human renal cancer.

Accumulating evidence indicates that microRNAs (miRNAs) play critical roles in regulating cellular processes, such as cell growth and apoptosis, as well as cancer progression and metastasis. Low expression of miR-497 has been observed in breast, colorectal and cervical cancers. Human bladder transitional cell carcinoma (BTCC) progression typically follows a complex cascade from primary malignancy to distant metastasis, but whether the aberrant expression of miR-497 in BTCC is associated with malignancy, metastasis or prognosis remains unknown. In the present study, we found that miR-497 was markedly downregulated in BTCC tissue samples when compared with that noted in adjacent normal tissues, and low expression of miR-497 was correlated with poor prognosis in BTCC patients. We also found that overexpression of miR-497 inhibited the proliferation, migration and invasion of bladder cancer cells by downregulating E2F3 (an miR-497 target gene) mRNA and protein and that siRNA against E2F3 inhibited cell proliferation, migration and invasion, which was similar to the effect of miR-497 overexpression in the BTCC cells. Our experimental data indicated that miR-497 mediates the in vitro proliferation, migration and invasion of BTCC cells. Together, these results suggest that miR-497 may represent a novel prognostic indicator, a biomarker for the early detection of metastasis and a target for gene therapy of BTCC.

BackgroundNetrin-1 and its receptor UNC5B play important roles in angiogenesis, embryonic development, cancer and inflammation. However, their expression patttern and biological roles in bladder cancer have not been well characterized. The present study aims to investigating the clinical significance of PKC α, netrin-1 and UNC5B in bladder cancer as well as their association with malignant biological behavior of cancer cells.MethodsNetrin-1 and UNC5B expression was examined in 120 bladder cancer specimens using immunohistochemistry and in 40 fresh cancer tissues by western blot. Immunofluorescence was performed in cancer cell lines. PKC α agonist PMA and PKC siRNA was employed in bladder cancer cells. CCK-8, wound healing assays and flow cytometry analysis were used to examine cell proliferation, migration and cell cycle, respectively.ResultsNetrin-1 expression was positively correlated with histological grade, T stage, metastasis and poor prognosis in bladder cancer tissues. Immunofluorescence showed elevated netrin-1 and decreased UNC5B expression in bladder cancer cells compared with normal bladder cell line. Furthermore, cell proliferation, migration and cell cycle progression were promoted with PMA treatment while inhibited by calphostin C. In addition, PMA treatment could induce while calphostin C reduce netrin-1 expression in bladder cancer cells.ConclusionsThe present study identified netrin-1/UNC5B, which could be regulated by PKC signaling, was important mediators of bladder cancer progression.

EIF2C, Dicer, and Drosha are microRNA-regulating machinery components, which participate in microRNA intracellular process and transfer. Our research demonstrated the expression and clinical role of the microRNA-regulating machinery in bladder cancer. EIF2C1, EIF2C2, Dicer, and Drosha mRNA and protein levels were analyzed in 100 bladder carcinomas and 50 normal bladder tissues using quantitative polymerase chain reaction and Western blotting. EIF2C2, Dicer, and Drosha mRNAs and proteins were overexpressed in carcinoma compared with normal tissues, whereas EIF2C1 mRNA and protein were not obviously different. Moreover, immunohistochemistry was used to detect the expressions of EIF2C2, Dicer, and Drosha in 100 bladder carcinomas. There were higher EIF2C2, Dicer, and Drosha expressions in carcinomas than in the adjacent normal tissues, positive correlations being noted with clinical stage, histopathologic grade, and recurrence. Higher EIF2C2, Dicer, and Drosha expressions were related to shorter cancer-specific survival and shorter recurrence-free survival. Multivariate Cox analysis showed that EIF2C2 was an important risk factor in bladder cancer. In conclusion, EIF2C2, Dicer, and Drosha are more highly expressed in bladder carcinoma, promote the development of bladder cancer, and suggested a poor prognosis. Their clinical role in bladder carcinoma merits further research.